Lab Notes: Hope for Men Yet

Study of the truncated Y chromosome has suggested to some researchers that the male of the species is due for the scrapheap. But now researchers led by Jennifer Hughes, PhD, of the Whitehead Institute for Biomedical Research in Cambridge, Mass., have found evidence that men may last longer than the so-called "Y-is falling" hypothesis suggests.

The X and Y chromosomes, the researchers noted in Nature, evolved from autosomal chromosomes between 200 and 300 million years ago. After that change, they essentially stopped the process of crossing over, by which chromosomes repair or replace damaged elements. Without that repair process, the human Y chromosome has lost all but 3% of its ancestral genes and some researchers thought the process was likely to continue in a straight line until they were all gone – and men with them.

But comparison of humans, chimps, and rhesus macaques suggests that Y chromosomes have lost their genes in five separate events and in each case the loss was rapid at first, but then flattened out and stopped. The analysis suggested that the human Y chromosome had almost completely stabilized some 30 million years ago – long before true humans evolved.

-- M.S.

Concussion Breeds Post-Trauma Fear

Even mild traumatic brain injury may predispose to later development of post-traumatic stress disorder (PTSD), an animal study suggested.

This was demonstrated in a series of experiments in which rats underwent surgically induced brain injury followed by Pavlovian fear conditioning, explained Michael S. Fanselow, PhD, of the University of California-Los Angeles, and colleagues. The animals were found to have upregulation of receptors in the amygdala, factors that are central to normal fear learning processes through effects on memory circuitry.

There has been considerable confusion as to a possible link between mild traumatic brain injury and subsequent PTSD, particularly in soldiers, because of the subjective nature of many symptoms of concussion. "For these reasons, mild traumatic brain injury has been labeled a silent epidemic, as well as the signature injury of the current theaters of combat," the researchers wrote in Biological Psychiatry.

This study provides a molecular explanation for the overlap in these two disorders, and can provide a laboratory model for further study, they noted.

-- N.W.

Lithium May Save Injured Nerves

Lithium chloride helped heal damaged nerves in a series of rat studies, French researchers said.

After the animals had facial and sciatic nerves crushed in a standardized way, treating them with lithium chloride promoted remyelination, the scientists reported in Proceedings of the National Academy of Sciences.

The drug is an inhibitor of glycogen synthase kinase 3-beta, the researchers explained, a class of drugs already known to have neuroprotective properties.

Because demyelination is central to multiple sclerosis as well as traumatic nerve injury, the study raises the possibility that lithium chloride might also help restore nerve function in MS patients.

-- J.G.

Mutated Gene Links SIDS With Arrhythmia

A mutation of the GJA1 gene has been linked with sudden infant death syndrome (SIDS), according to a study in Circulation.

"It is the first molecular and functional evidence implicating a GJA1 mutation as a novel pathogenic substrate for SIDS," wrote David W. Van Norstrand, BS, from the Mayo Clinic in Rochester, Minn., and colleagues.

They found two novel mutations to the GJA1-encoded protein connexin43 (Cx43), the predominant ventricular gap junction connexin and a key to steady contractions. Previous studies have linked mutations in Cx43 (and Cx40) to atrial fibrillation and sudden cardiac arrest.

The results, gleaned from DNA analysis of 292 SIDS cases, contribute "to the growing body of literature implicating cardiac arrhythmias as the cause of a subset of deaths caused by SIDS," researchers said.

-- C.K.

The Naked Truth About Brain Hypoxia

The ability to control calcium influx might offer a strategy to save brain tissue during hypoxic conditions, according to studies of subterranean naked mole rats.

When exposed to experimental hypoxia, hippocampal tissue from the rats had significantly less accumulation of calcium than did tissue from laboratory mice. The observation offers a clue as to how large colonies of naked mole rats survive underground in an oxygen-poor, carbon dioxide- and ammonia-rich environment, as reported online in PLoS ONE.

The brains of human newborns have a similar protective mechanism, which disappears as they grow older.

The laboratory findings could point the direction toward therapies to protect the human adult brain from the effects of oxygen deprivation, Thomas J. Park, PhD, of the University of Illinois at Chicago, and co-authors wrote in their summation.

-- C.B.

Striking Down Inflammation

Researchers have developed a compound that blocks excessive reactive oxygen species production, which may some day be used to treat human diseases caused by inflammation.

Previous attempts to target excessive inflammation in this manner have been unsuccessful because of toxicity caused by effects on other molecular processes.

Yi Zheng, PhD, of Cincinnati Children's Hospital Medical Center, and colleagues discovered the current compound – called Phox-I -- by using computer-assisted screening to search through 350,000 drug-like compounds.

Phox-I targets a single component of the NOX2 enzyme complex, which drives the production of reactive oxygen species in white blood cells. The compound prevents a NOX2 enzyme from binding to the Rac GTPase regulatory pathway, which blocks NOX2 activation and the resulting inflammation.

Although the compound worked in normal human blood cells, leukemic cells, and mouse blood cells without causing any toxicity, more testing needs to be done before human trials can begin, Zheng said in a statement.

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